Detection and treatment of infections with immunoconjugates

Abstract

A method of targeting a diagnostic or therapeutic agent to a focus of infection comprises injecting a patient infected with a pathogen parenterally with an antibody conjugate which specifically binds to an accessible epitope of the pathogen or of a pathogen-associated antigen accreted at the focus of infection, the antibody conjugate further comprising a bound diagnostic or therapeutic agent for detecting, imaging or treating the infection. Polyspecific composite conjugates enhance the efficacy of the method, which is especially useful for treating infections that are refractory towards systemic chemotherapy.

What is claimed is: 
     
       1. A method of targeting a polyspecific diagnostic agent to a focus of infection, which comprises parenterally injecting a patient infected with a pathogen with an effective amount of a polyspecific diagnostic antibody conjugate comprising an immunoreactive composite of a plurality of chemically linked antibodies or antibody fragments which specifically bind to a plurality of epitopes on a single species of pathogen or an antigen shed by said pathogen or resulting from the fragmentation or destruction of said pathogen, wherein said conjugate further comprises at least one diagnostic agent. 
     
     
       2. The method of claim 1, wherein said agent is a diagnostic agent selected from the group consisting of a radioisotope and a magnetic resonance image enhancing agent. 
     
     
       3. The method of claim 1, wherein said antibody conjugate specifically binds to an accessible epitope of said pathogen or said antigen which is not saturated or blocked by the patient's native antibodies. 
     
     
       4. The method of claim 1, wherein said pathogen is a virus. 
     
     
       5. The method of claim 4, wherein said virus is an RNA virus. 
     
     
       6. The method of claim 4, wherein said virus is a DNA virus. 
     
     
       7. The method of claim 4, wherein said virus is selected from the group consisting of human immunodeficiency virus (HIV), herpes virus, cytomegalovirus, rabies virus, influenza virus, hepatitis B virus, Sendai virus, feline leukemia virus, Reo virus, polio virus, human serum parvo-like virus, simian virus 40, respiratory syncytial virus, mouse mammary tumor virus, Varicella-Zoster virus, Dengue virus, rubella virus, measles virus, adenovirus, human T-cell leukemia viruses, Epstein-Barr virus, murine leukemia virus, mumps virus, vesicular stomatitis virus, Sindbis virus, lymphocytic choriomeningitis virus, wart virus and blue tongue virus. 
     
     
       8. The method of claim 1, wherein said pathogen is a bacterium. 
     
     
       9. The method of claim 8, wherein said bacterium is selected from the group consisting of Streptococcus agalactiae, Legionella pneumophilia, Streptococcus pyogenes, Escherichia coli, Neisseria gonorrhoeae, Neisseria meningitidis, Pneumococcus, Hemophilis influenzae B, Treponema pallidum, Lyme disease spirochetes, Pseudomonas aeruginosa, Mycobacterium leprae, Brucella abortus, Mycobacterium tuberculosis and Tetanus toxin. 
     
     
       10. The method of claim 1, wherein said pathogen is a protozoan. 
     
     
       11. The method of claim 10, wherein said protozoan is selected from the group consisting of Plasmodium falciparum, Plasmodium vivax, Toxoplasma gondii, Trypanosoma rangeli, Trypanosoma cruzi, Trypanosoma rhodesiensei, Trypanosoma brucei, Schistosoma mansoni, Schistosoma japanicum, Babesia bovis, Elmeria tenella, Onchocerca volvulus, Leighmania tropica, Trichinella spiralis, Onchocerca volvulus, Theileria parva, Taenia hydatigena, Taenia ovis, Taenis sagenata, Echinococcus granulosus and Mesocestoides corti. 
     
     
       12. The method of claim 1, wherein pathogen is a helminth. 
     
     
       13. The method of claim 1, wherein said pathogen is mycoplasma. 
     
     
       14. The method of claim 13, wherein said mycoplasma is selected from the group consisting of Mycoplasma arthritidis, M. hyorhinis, M. orale, M. arginini, Acholeplasma laidlawii, M. salivarium and M. pneumoniae. 
     
     
       15. The method of claim 1, which further comprises administering to said patient, at a time after administration of said conjugate sufficient to optimize uptake of said conjugate at the site of said infection, an amount of a second antibody that specifically binds to said conjugate sufficient to reduce the amount of said conjugate in circulation by 10-85% within 2-72 hours. 
     
     
       16. The method of claim 1, wherein said polyspecific antibody conjugate comprises chemically linked antibody or antibody fragment components of an antiserum. 
     
     
       17. The method of claim 16, wherein said antiserum is affinity purified by removal of antibodies which bind to said antigen circulating at a significant level in the patient's bloodstream. 
     
     
       18. The method of claim 16, wherein said antiserum is affinity purified by contact with bound pathogen or bound antigen, and subsequent recovery of antiserum enriched in antibodies that bind to said pathogen or said antigen. 
     
     
       19. The method of claim 1, wherein said polyspecific antibody conjugate comprises chemically linked monoclonal antibodies or fragments thereof. 
     
     
       20. A polyspecific diagnostic antibody conjugate for targeting a focus of infection, comprising an immunoreactive composite of a plurality of chemically linked antibodies or antibody fragments which specifically bind to a plurality of epitopes on a single species of pathogen or an antigen shed by said pathogen or resulting from the fragmentation or destruction of said pathogen, wherein said conjugate further comprises at least one diagnostic agent. 
     
     
       21. The conjugate of claim 20, wherein said chemically linked antibodies or antibody fragments are components of an antiserum. 
     
     
       22. The conjugate of claim 21, wherein said antiserum is affinity purified by removal of antibodies which bind to said antigen circulating at a significant level in the patient's bloodstream. 
     
     
       23. The conjugate of claim 21, wherein said antiserum is affinity purified by contact with bound pathogen or bound antigen, and subsequent recovery of antiserum enriched in antibodies that bind to said pathogen or said antigen. 
     
     
       24. The conjugate of claim 20, wherein said polyspecific antibody conjugate comprises chemically linked monoclonal antibodies or fragments thereof. 
     
     
       25. A kit for use in preparing a sterile injectable preparation for targeting a focus of infection in a human patient, comprising in suitable containers, the polyspecific antibody conjugate of claim 20 and a pharmacologically acceptable sterile injection vehicle. 
     
     
       26. The kit of claim 25, wherein said chemically linked antibodies or antibody fragments are components of an antiserum. 
     
     
       27. The kit of claim 26, wherein said antiserum is affinity purified by removal of antibodies which bind to said antigen circulating at a significant level in the patient's bloodstream. 
     
     
       28. The kit of claim 26, wherein said antiserum is affinity purified by contact with bound pathogen or bound antigen, and subsequent recovery of antiserum enriched in antibodies that bind to said pathogen or said antigen. 
     
     
       29. The kid of claim 25, wherein said polyspecific antibody conjugate comprises chemically linked monoclonal antibodies or fragments thereof.